When predicting atrial fibrillation, think 'scene of calamity'!

This editorial refers to ‘Prognostic value of left atrial expansion index and exercise-induced change in atrial natriuretic peptide as long-term predictors of atrial fibrillation recurrence’ by M. Govindan et al., on page 1302 Predicting events in patients with atrial fibrillation (AF) comes in two flavours: predicting events linked to the atria (such as AF recurrence after cardioversion or ablation, or AF progression from paroxysmal to persistent), and events whose origin may be remote from the atria such as stroke, heart failure, or myocardial infarction. Mechanisms linked to the ‘scene of calamity’, i.e. the atrial wall itself, may appear stronger predictors for AF than characteristics remote from the atria such as age of the patient and underlying ventricular disease, even when combined in a risk score like HATCH, a score used to predict AF progression.1 In this respect, the findings as presented in the current issue of the Journal2 are noteworthy as atrial N-terminal proatrial natriuretic peptide (NTproANP) production and left atrial expansion index (LAEI) were independently linked to the recurrence of persistent AF after cardioversion, whereas conventional ‘remote’ parameters were not. Intuitively, these parameters make sense as both relate to integrity of the atrial wall and its function. If the atrial wall is relatively healthy, ANP may be released in sufficient amounts after an increase in wall tension ([atrial pressure × atrial diameter]/wall thickness). The latter may occur after imposing a haemodynamic burden (exercise stress test or a temporarily increased diastolic pressure, e.g. in acute heart failure) but less so, if at all, with a high atrial rate during AF.3 Similarly, a high LAEI—at a relatively low maximum atrial volume—indicates a healthy atrial wall with low stiffness (in addition to normal left ventricular diastolic function). In turn, and further to the above, a normally functioning atrial wall is associated with maintenance of sinus rhythm as it will not contain a large amount of atrial substrate to maintain AF. Lack of an exercise-induced rise in ANP levels has been shown previously to predict adverse arrhythmia outcome after cardiovrsion of AF.4,5 Similarly, LAEI has been reported recently as a significant predictor of AF post-coronary-artery bypass graft.6 In that study average values of LAEI were 50 and 90% in patients with and without post-coronary-artery bypass graft AF, respectively. These values are much higher than those seen in this study, probably relating to the fact that in Wang et al.'s6 study patients were in sinus rhythm at the time of measurement. It is questionable whether loss of atrial myocytes is the main reason for absent ANP rise during exercise in patients with AF recurrence, as was suggested by the authors. Alternatively, higher average atrial pressure at rest associated with higher resting ANP levels—as indeed were found in these patients—may have precluded a significant further rise in atrial wall stress on exercise, thus explaining absent ANP rise. Typically, such atria harbour the substrate for (recurrence of) AF. Considering the above, an absent ANP secretion on exercise and a low LAEI share in part the same pathophysiological mechanism. However, LAEI and ANP rise on exercise were only weakly correlated, suggesting their independent predictive value. Nevertheless, an interaction between both parameters in terms of enhancement of each other's predictive power when combined may exist but was not reported. Relapses occur after cardioversion of persistent AF either as subacute recurrences within 1 month, or as late re-occurrences beyond that time point.7 The mechanisms underlying these two types are different: subacute recurrences are much more frequent and may be suppressed by class IC drugs or amiodarone combined with either renin–angiotensin system blockers or verapamil, whereas such combinations do not reduce late recurrences.8–10 In this study, recurrences were very frequent in the first month after cardioversion (subacute recurrences, ∼40% of all patients, around two-thirds of all recurrences) and only 10% between 1 and 3 months and an additional 10% the rest of the year. The predictive value of LAEI and NTproANP response during exercise might have been tested for subacute recurrences separately especially as the arrhythmogenic mechanism may differ from that underlying late reoccurrences, thus avoiding a mixed-bag analysis. In addition, the possible confounding effect of calcium channel blockers, amiodarone, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers (the latter not reported) and their combinations with respect to changing arrhythmia outcome might have been considered to enhance the predictive ability of both parameters. The fact that calcium-channel blockers were relatively frequently used by patients with a recurrence may reflect underlying hypertension and is difficult to interpret in a non-randomized study. Will these parameters be used to select symptomatic AF patients for cardioversion? This depends on their robustness to predict, ease of use, and importance of the predicted clinical outcome. Indeed further confirmation in larger studies is needed. Left atrial expansion index is easy to obtain. In contrast, the NTproANP response to exercise seems time consuming and potentially costly. Predicting outcome of cardioversion may be considered mot very relevant by clinicians. Electrical cardioversion is a quite compelling procedure: success in terms of production of sinus rhythm can be seen immediately and recurrences do not happen commonly before discharge, i.e. are only seen during follow-up. The latter means that the recurrence is seen disconnected in time from the cardioversion procedure itself which makes it an acceptable procedure for both doctor and patient despite a high recurrence rate. Whether LAEI or ANP changes on exercise will appear predictive of other arrhythmic events including AF progression or arrhythmia outcome after AF ablation remains to be seen. Also it is at present unclear as to whether these parameters may be used to predict new onset AF in patients with hypertension or heart failure at high risk of developing AF. Such predictive tests may enhance primary stroke prevention strategies in those patients while it is unclear as to whether they may also help to ameliorate AF substrate progression. It is clear that the present results are an important step forward by promoting assessment of AF prognosis at the scene of calamity, i.e. at the atrial level. Nevertheless, many questions remain and need to be investigated to improve atrial predictors. Conflict of interest: none declared.